Development of Quantitative PET Imaging Probes for Neuroinflammation

神经炎症定量 PET 成像探针的开发

• 批准号: G0900891/2
• 负责人: Federico Turkheimer
• 金额: $ 29.74万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900891%2F2
• 关键词: Development; Quantitative; PET; Imaging; Probes

Inflammation is a protective attempt by the immune response of the organism to remove the injurious stimuli as well as to initiate the healing process for the tissue. The inflammatory process is generally beneficial but an inflammation that runs unchecked can also lead to a host of diseases, such as hay fever, atherosclerosis, and rheumatoid arthritis. It is for this reason that inflammation is normally closely regulated by the body.The brain and spinal cord are considered ?immune privileged? tissues in that they are separated from the rest of the body by a series of endothelial cells known as the blood-brain barrier, which prevent most infections from reaching the vulnerable nervous tissue. For this reason, inflammation in the CNS (Neuroinflammation) is mediated by a unique cell type, microglia. Microglia are part of the non-neuronal part of the cell population in the brain called glia, the other glial cell being the astrocytes and the oligodendrocytes. Quiescent microglia have a ramified morphology as they are constantly moving and analyzing the CNS for damaged neurons, plaques, and infectious agents; whenever an anomaly is detected, microglia enter an active state and undergo several morphological changes including the thickening and retraction of branches, the expression of immunomolecules, the secretion of cytotoxic factors, recruitment molecules and pro-inflammatory signaling molecules. Microglial activation is therefore present early in any pathological state of the brain and the in-vivo detection of microglial activation is a key diagnostic aim. Besides, microglia chronic activation has also been suggested as a key factor in the inception and/or progression of neurodegenerative diseases like Alzheimer?s disease and Parkinson?s disease. This project aims at delivering an optimal imaging biomarker for microglia using Positron Emission Tomography (PET) technology. PET is a Nuclear Medicine modality that is able to image the distribution of radioactive labelled compounds. The interest in imaging microglia with PET radiotracers is such that more than 50 radiotracers targeting microglia are now proposed world-wide. In the context of this training proposal, we will test the most promising PET microglia tracers, devise appropriate data-processing procedures and metrics that will allow the selection of the optimal marker to be used in the future in diagnostics, research and drug development.

炎症是机体免疫反应的一种保护性尝试，目的是清除有害刺激，并启动组织的愈合过程。炎症过程通常是有益的，但不加控制的炎症也会导致一系列疾病，如花粉热、动脉粥样硬化和类风湿性关节炎。正因为如此，炎症通常受到身体的密切调控。大脑和脊髓被认为是免疫特权？组织，因为它们与身体的其他部分被一系列被称为血脑屏障的内皮细胞隔开，这些内皮细胞防止大多数感染到达脆弱的神经组织。因此，中枢神经系统的炎症是由一种独特的细胞类型--小胶质细胞介导的。小胶质细胞是大脑中称为胶质细胞的非神经性部分的一部分，另一种胶质细胞是星形胶质细胞和少突胶质细胞。静止的小胶质细胞在不断移动和分析中枢神经系统中受损的神经元、斑块和感染性物质时，具有分叉的形态；每当检测到异常时，小胶质细胞进入活跃状态，并经历几种形态变化，包括分支增粗和回缩，免疫分子的表达，细胞毒性因子的分泌，募集分子和促炎信号分子。因此，小胶质细胞的激活在大脑的任何病理状态中都是早期存在的，体内检测小胶质细胞的激活是一个关键的诊断目标。此外，小胶质细胞的慢性激活也被认为是阿尔茨海默病、S病和帕金森S病等神经退行性疾病发生和/或发展的关键因素。该项目旨在利用正电子发射断层扫描(PET)技术为小胶质细胞提供最佳的成像生物标记物。PET是一种核医学模式，能够对放射性标记化合物的分布进行成像。人们对用PET放射性示踪剂对小胶质细胞进行成像的兴趣如此之大，以至于现在全世界都提出了50多种靶向小胶质细胞的放射性示踪剂。在这项培训计划的背景下，我们将测试最有希望的PET小胶质细胞示踪剂，设计适当的数据处理程序和衡量标准，以便选择未来用于诊断、研究和药物开发的最佳标记物。